RESUMO
INTRODUCTION: Single nucleotide polymorphisms (SNP) in the fat mass and obesity-associated (FTO) gene have been associated with type 2 diabetes (T2D) and its complications. The aim of the present research was to investigate which and how (directly or indirectly) clinical and metabolic variables mediate the association between fat mass and the FTO gene and early chronic kidney disease (CKD) in individuals with T2D. METHODS: This cross-sectional study was conducted in a sample of 236 participants with T2D (53.4% women, mean age 60 ± 10 years). DNA samples were genotyped for the rs7204609 polymorphism (C/T) in the FTO gene. Clinical, anthropometric, and metabolic data were collected. Path analysis was used to evaluate the associations. RESULTS: Of the sample, 78 individuals with T2D had CKD (33%). Presence of the risk allele (C) was higher among participants with CKD (21.8 vs. 10.8%; p = 0.023). This polymorphism was positively associated with higher waist circumference, which in turn was associated with higher glycated hemoglobin and higher blood pressure. A higher blood-pressure level was associated with higher urinary albumin excretion (UAE) and as expected, higher UAE was associated with CKD. Path analysis showed an indirect relationship between the FTO gene and early CKD, mediated by waist circumference, blood-pressure levels, and UAE. CONCLUSIONS: These findings suggest that the C allele may contribute to genetic susceptibility to CKD in individuals with T2D through the presence of central obesity, hypertension, and high albuminuria.
Assuntos
Diabetes Mellitus Tipo 2 , Hipertensão , Insuficiência Renal Crônica , Idoso , Albuminúria/genética , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Índice de Massa Corporal , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/genética , Obesidade Abdominal , Polimorfismo de Nucleotídeo Único , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/genéticaRESUMO
The fat mass and obesity-associated gene (FTO) has been extensively reported in the literature related to nutritional status, but there has been limited description of the genetic contribution to obesity risk during childhood and adolescence, especially in Latin Americans. This study aims to associate the rs9939609 polymorphism, of the FTO gene, with changes in nutritional status in Brazilian schoolchildren followed for 3 years. A longitudinal study was conducted with 355 schoolchildren, aged 7-15 years in 2011/2012 and subsequently re-evaluated in 2014/2015. Nutritional (obesity) status was classified by identifying those exceeding recommended thresholds for waist circumference (WC), waist-to-height ratio (WHtR), body mass index (BMI), and body fat percentage (BF%). The rs9939609 polymorphism was genotyped by a real-time polymerase chain reaction. Relative risk (RR with 95% confidence interval) of obesity status by FTO gene polymorphism was calculated by Poisson regression. The risk group was determined for genotypes with the allele A polymorphism, and regression models were adjusted for age, sex, height, ethnicity, and geographical location. Considering the longitudinal changes in status over the 3-year follow-up, the RR of developing a WC exceeding the threshold recommended (WC >75th age and sex-standardized percentile), or remaining with this condition, was higher in children with AT/AA genotype. For WC, the RR was 1.66 (1.07; 2.58) in crude analysis and 1.17 (1.01; 1.35) following adjustment for age (years), gender, ethnicity, and geographical location. The comparative risk of abdominal obesity, assessed by WHtR (not recommended threshold ≥0.50), was 53% and 8%, respectively, higher in AT/AA compared to TT genotype.Conclusion: This is one of the first longitudinal investigations to show a significant association between the A allele of the rs9939609 polymorphism and individuals with higher than recommended WC and WHtR measures in Brazilian children and adolescents. What is known: ⢠The FTO has an effect on increases in body mass index (BMI) among children and adolescents. ⢠It established the association between FTO and overweight/obesity in Caucasians. What is new: ⢠The presence of the risk allele of rs9939609 (FTO gene) polymorphism is associated with increased abdominal fat in Brazilian schoolchildren. ⢠Was detected an association between FTO gene polymorphism (rs9939609) with WC in follow-up cohort and changes in WC and WHtR follow-up over 3 years, during childhood and adolescence growth.